Prevention of thrombosis with anticoagulants, such as heparin or coumadin, is critical for treatment of many diseases and conditions (e.g., atrial fibrillation, sepsis, trauma, prosthetic heart valves, various coagulapathies or other bleeding disorders) as well as for many life-saving procedures, including dialysis, hemofiltration, extracorporeal oxygenation (ECMO), angioplasty, intravenous fluid delivery, apheresis and collection of blood samples for analysis or culture. As thrombosis can result from activation of platelets as well as the coagulation cascade, anticoagulation therapy is typically supplemented by anti-platelet therapy. It would therefore be extremely helpful to be able to monitor global anticoagulation in real-time in the clinic because coagulation responses to variations in anticoagulant levels and platelet numbers can vary significantly among patients and in the same patient at different times. However, it is currently difficult to quickly and quantitatively ascertain the degree and efficiency of whole blood anti-coagulation and anti-platelet therapies, and there is no reliable method to do it rapidly at the bedside, having the possibility of using native blood.
Patients who have bleeding or clotting problems are now routinely monitored using Prothrombin Time (PT) and Activated Clotting Time (ACT)/Activated Partial Clotting Time (APTT) tests, which provide semi-quantitative measures of the extrinsic or intrinsic coagulation pathways respectively. However, the results produced by these assays can vary considerably depending on sample preparation, anticoagulation tubes, addition of activators, equipment, and user expertise. As a result, measurements of the same sample carried out at different sites or on different days often produce different results. The specificity and sensitivity of these tests are also poor and often result in false positive or negative cases in the clinic. Moreover, PT, ACT and APTT assays do not provide information on platelet function and therefore, do not serve as global coagulation tests. Because of the limitations of conventional blood clotting time tests, new point-of-care monitoring systems, such as thromboelastography (TEG) and rotation thromboelastometry (ROTEM) devices, have started to be integrated into clinical laboratories. These devices are able to provide greater information about hemostasis because they measure the cumulative contribution of plasma, platelets, leukocytes and red blood cells to the clotting response. These tests, however, measure clotting characteristics under static conditions (no flow) and hence, they are limited in their clinical utility with respect to platelet and endothelial cell functions, which are highly sensitive to physical forces, including pressure and flow. For example, fluid shear stresses and gradients of shear stresses in blood have a major impact on platelet activation and thrombosis and thus, coagulation monitors that do not incorporate fluid dynamics fail to accurately assess blood coagulation physiology as it occurs in the vasculature of a living patient.